Several infections are successfully combated by the immune system of a mammal such as a human being. However, in some instances, bacteria, fungi, or viruses are not always cleared, which may cause localised or generalised acute infections. This is a serious concern at perinatal-, burn, or intensive care units, and in immunocompromised individuals. In other cases, a continuous bacterial persistence at epithelial surfaces may cause or aggravate chronic disease. In humans, this is exemplified by chronic skin ulcers, atopic dermatitis and other types of eczema, acne, or genitourinary infections.
Symptomatic infections may be treated by various medicaments. Some diseases may also be combated by for instance vaccines. However, vaccines are not always the best treatment option and for certain microorganisms no vaccine is available. When no protection is available treatment of the disease is pursued. Often the treatment is performed by the use of an antibiotic agent, which kills the microbe. However, during the last years several microbes have become resistant against antibiotic agents. Most likely, resistance problems will increase in the near future. Additionally, several individuals have developed allergy against the antibiotic agent, thereby reducing the possibility to effectively use certain antibiotic agents.
Epithelial surfaces of various organisms are continuously exposed to bacteria. During recent years the innate immune system, based on antibacterial peptides has been attributed important roles in the initial clearance of bacteria at biological boundaries susceptible to infection (Lehrer, R. I., and Ganz, T. (1999) Curr Opin Immunol 11: 23-27, Boman, H. G. (2000) Immunol. Rev. 173, 5-16). Antimicrobial peptides kill bacteria by permeating their membranes, and thus the lack of a specific molecular microbial target minimizes resistance development.
Several antimicrobial peptides and proteins, unrelated to the herein described peptides are known in the art.
U.S. Pat. No. 6,503,881 disclose cationic peptides being an indolicidin analogue to be used as an antimicrobial peptide. The cationic peptides being derived from different species, including animals and plants.
U.S. Pat. No. 5,912,230 disclose anti-fungal and anti-bacterial histatin-based peptides. The peptides being based on defined portions of the amino acid sequences of naturally occurring human histatins and methods for treatment of fungal and bacterial infections.
U.S. Pat. No. 5,717,064 disclose methylated lysine-rich lytic peptides. The lytic peptides being tryptic digestion resistant and non-natural. The lytic peptides are suitable for in vivo administration.
U.S. Pat. No. 5,646,014 disclose an antimicrobial peptide. The peptide was isolated from an antimicrobial fraction from silkworm hemolymph. The peptide exhibits excellent antimicrobial activity against several bacterial strains, such as Escherichia coli, Staphylococcus aureus and Bacillus cereus. 
McCabe et al., J.Biol.Chem. Vol 277:27477-27488, 2002, describes an 37 kDa antimicrobial and chemotactic protein, azurocidin, containing the heparin binding consensus motifs XBBXBX and XBBBXXBX.
WO2004016653 disclose a peptide based on the 20-44 sequence of azurocidin. This peptide contains a loop structure linked by disulfide bridges.
U.S. Pat. No. 6,495,516 and related patents, disclose peptides based on the bactericidal 55 kDa protein bactericidal/permeability increasing protein (BPI). The peptides exerted antimicrobial effects as well as had heparin and LPS-neutralizing capacity.
WO 01/81578 discloses numerous sequences encoding G-coupled protein-receptor related polypeptides, which may be used for numerous diseases.
WO 00/27415 discloses peptides being suitable for inhibition of angiogenesis. The peptides being analogous of high molecular weight kininogen 5. The BLASTp search shows sequences, which are conserved or have similarities among different species such as kininogen without any indication of the function of such conserved regions or if they at all have any function as small peptides.
At present, over 700 different antimicrobial peptide sequences are known (www.bbcm.univ.trieste.it/˜tossi/search.htm), including cecropins, defensins magainins and cathelicidins.
Even though there is a huge amount of antimicrobial peptides available today there is still an increased need of new improved antimicrobial peptides. Antimicrobial peptides which can be used to combat microbes and being resistant or tolerant against antibiotic agents and/or other antimicrobial agents. Additionally, there is a need for new antimicrobial peptides, which are non-allergenic when introduced into mammals such as human beings. Bacteria have encountered endogenously produced antimicrobial peptides during evolution without induction of significant resistance.